Identification of Immunological Parameters as Predictive Biomarkers of Relapse in Patients with Chronic Myeloid Leukemia on Treatment-Free Remission.
Identification of Immunological Parameters as Predictive Biomarkers of Relapse in Patients with Chronic Myeloid Leukemia on Treatment-Free Remission.
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DOI：
10.3390/jcm10010042
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发表时间：
2020-12-25
影响因子：
3.9
通讯作者：
Coiras M
中科院分区：
文献类型：
--
作者：
Vigón L;Luna A;Galán M;Rodríguez-Mora S;Fuertes D;Mateos E;Piris-Villaespesa M;Bautista G;San José E;Rivera-Torres J;Steegmann JL;de Ory F;Pérez-Olmeda M;Alcamí J;Planelles V;López-Huertas MR;García-Gutiérrez V;Coiras M
BCR-ABL是一种异常的酪氨酸激酶，可导致慢性粒细胞白血病（CML）。酪氨酸激酶抑制剂（TKI）主要基于抑制BCR-ABL而诱导强效抗白血病反应，但它们也增加自然杀伤细胞（NK）和CD 8 + T细胞的活性。几年后，患者可能会因持续的深层分子反应而中断治疗。由于未知的原因，一半的患者在治疗中断期间复发，而另一些患者在几年内对残留的白血病细胞保持有效的控制。在这项研究中，分析了与持续抗白血病控制相关的几个免疫学参数。根据我们的研究结果，与抗白血病控制不良更相关的特征如下：低水平的细胞毒性细胞，如NK、（自然杀伤T）NKT和CD 8 ±TCRγβ+ T细胞; NK和NKT细胞表面活化受体表达低; NK细胞的促炎细胞因子或蛋白酶合成受损; HLA-E*0103纯合性和KIR单倍型BX。随机森林算法预测90%的准确性，根据这些参数的复发或非复发组的CML患者的分类。因此，这些特征可能是有用的生物标志物预测的CML复发的患者，是候选人启动治疗中止。
BCR-ABL is an aberrant tyrosine kinase responsible for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKIs) induce a potent antileukemic response mostly based on the inhibition of BCR-ABL, but they also increase the activity of Natural Killer (NK) and CD8+ T cells. After several years, patients may interrupt treatment due to sustained, deep molecular response. By unknown reasons, half of the patients relapse during treatment interruption, whereas others maintain a potent control of the residual leukemic cells for several years. In this study, several immunological parameters related to sustained antileukemic control were analyzed. According to our results, the features more related to poor antileukemic control were as follows: low levels of cytotoxic cells such as NK, (Natural Killer T) NKT and CD8±TCRγβ+ T cells; low expression of activating receptors on the surface of NK and NKT cells; impaired synthesis of proinflammatory cytokines or proteases from NK cells; and HLA-E*0103 homozygosis and KIR haplotype BX. A Random Forest algorithm predicted 90% of the accuracy for the classification of CML patients in groups of relapse or non-relapse according to these parameters. Consequently, these features may be useful as biomarkers predictive of CML relapse in patients that are candidates to initiate treatment discontinuation.
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影响因子：
78.8
作者：
Bocchia, Monica;Defina, Marzia;Lauria, Francesco
通讯作者：
Lauria, Francesco
影响因子：
1.1
作者：
D'Antonio, Jocelyn
通讯作者：
D'Antonio, Jocelyn
影响因子：
4
作者：
Dumas, Pierre-Yves;Berard, Emilie;Mahon, Francois-Xavier
通讯作者：
Mahon, Francois-Xavier
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T
影响因子：
7.3
作者：
Cisneros E;Moraru M;Gómez-Lozano N;López-Botet M;Vilches C
通讯作者：
Vilches C